NM_144997.7(FLCN):c.1615dup (p.Leu539fs) AND Birt-Hogg-Dube syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 28, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003607522.2

Allele description [Variation Report for NM_144997.7(FLCN):c.1615dup (p.Leu539fs)]

NM_144997.7(FLCN):c.1615dup (p.Leu539fs)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.1615dup (p.Leu539fs)

HGVS:

NC_000017.11:g.17213781dup
NG_008001.2:g.28409dup
NM_001353229.2:c.1669dup
NM_001353230.2:c.1615dup
NM_001353231.2:c.1615dup
NM_144997.7:c.1615dupMANE SELECT
NP_001340158.1:p.Leu557fs
NP_001340159.1:p.Leu539fs
NP_001340160.1:p.Leu539fs
NP_659434.2:p.Leu539Profs
NP_659434.2:p.Leu539fs
LRG_325t1:c.1614dup
LRG_325:g.28409dup
LRG_325p1:p.Leu539Profs
NC_000017.10:g.17117093_17117094insG
NC_000017.10:g.17117095dup
NM_144997.5:c.1614dup
NM_144997.5:c.1615dupC

Protein change:

L539fs

Molecular consequence:

NM_001353229.2:c.1669dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353230.2:c.1615dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353231.2:c.1615dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144997.7:c.1615dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Birt-Hogg-Dube syndrome
Synonyms:: BHD syndrome; Birt Hogg Dubé syndrome
Identifiers:: MONDO: MONDO:0800444; MedGen: C0346010; Orphanet: 122; OMIM: PS135150

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004370158	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28558743, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004370158

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 28, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dubé syndrome.

Liu Y, Xu Z, Feng R, Zhan Y, Wang J, Li G, Li X, Zhang W, Hu X, Tian X, Xu KF, Zhang X.

Orphanet J Rare Dis. 2017 May 30;12(1):104. doi: 10.1186/s13023-017-0656-7.

PubMed [citation]

PMID:: 28558743
PMCID:: PMC5450333

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004370158.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change results in a frameshift in the FLCN gene (p.Leu539Profs*63). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the FLCN protein and extend the protein by 21 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1776474). This variant disrupts a region of the FLCN protein in which other variant(s) (p.Trp553*) have been determined to be pathogenic (PMID: 28558743; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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